Background

Lead (Pb) is known to induce detrimental health effects in exposed populations, including hematotoxicity and genotoxicity. Complete blood count (CBC) is a cost-effective and easy way to determine toxicity, and variations in proportion of different types of leukocytes: neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are further evidence of hematotoxicity. However, few studies have been conducted to systematically evaluate effects of occupational Pb exposure on NLR and LMR, and their associations with genotoxicity.

Objectives

Our study was aimed to systematically assess the effects of current occupational Pb exposure on NLR and LMR, and their associations with genotoxicity.

Methods

Our investigation was performed on 1176 workers from a newly built battery factory in North China. The workers had just entered their current job position in recent years and most of them had no previous history of occupational exposure to Pb. Blood lead levels (BLLs) and leukocytes indices were detected for all participants. Cytokinesis-blocked micronucleus assay (MN; n = 675) and alkaline comet assay (% tail DNA; n = 869) were used to assess genotoxicity. Multivariate linear and Poisson regression analyses were conducted to examine associations between leukocytes indices, genotoxic biomarkers and BLLs with adjustment for covariates. Spearman correlation and mediation analyses were used to investigate relationships between NLR and genotoxicity.

Results

Among all the exposed workers, NLR increased with increasing BLLs. However, WBC and LMR did not change significantly. Significant and dose-dependent increases in both MN frequencies and % tail DNA were observed among groups with different exposure doses. Compared with the normal NLR group (1.48 ≤ NLR < 4.58), the high NLR group (NLR ≥ 4.58) had higher % tail DNA. In addition, there was a significant and positive association between NLR and % tail DNA among all the workers, and % tail DNA mediated 15% of the effect of Pb on increasing NLR.

Conclusion

Our large-scale population study shows that Pb exposure increased NLR and induced genotoxicity. There was an association between elevated NLR and DNA damage. In addition, the mediation effect of % tail DNA on the relationship between BLLs and NLR provided mechanistic evidence that certain mechanisms, e.g. inflammation, may be involved in elevation of NLR from Pb exposure. Therefore, NLR may be a convenient and sensitive biomarker for indication of Pb toxicity. Further studies are needed to validate the proposed mechanism and NLR as a biomarker.

中文翻译：

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早期职业接触铅对中性粒细胞与淋巴细胞的比率和遗传毒性

背景

已知铅（Pb）会在暴露人群中引起有害的健康影响，包括血液毒性和遗传毒性。全血细胞计数（CBC）是确定毒性的一种经济高效且简便的方法，不同类型白细胞（嗜中性白细胞与淋巴细胞之比（NLR）和淋巴细胞与单核细胞之比（LMR））的比例存在差异血液毒性。但是，很少进行研究来系统地评估职业性铅暴露对NLR和LMR的影响以及它们与遗传毒性的关系。

目标

我们的研究旨在系统地评估当前职业铅暴露对NLR和LMR的影响以及它们与遗传毒性的关系。

方法

我们对来自华北新建电池厂的1176名工人进行了调查。近年来，这些工人刚刚进入他们目前的工作岗位，其中大多数人以前没有职业性的铅暴露史。所有参与者均检测到血铅水平（BLLs）和白细胞指数。胞质分裂阻滞微核试验（MN； n = 675）和碱彗星试验（％尾巴DNA； n = 869）用于评估遗传毒性。进行了多元线性和泊松回归分析，以检查白细胞指数，遗传毒性生物标志物和BLL之间的关联，并调整了协变量。使用Spearman相关性和中介分析来研究NLR与遗传毒性之间的关系。

结果

在所有暴露的工人中，NLR随着BLL的增加而增加。但是，WBC和LMR没有明显变化。在具有不同暴露剂量的组中，观察到MN频率和尾巴DNA百分比显着且剂量依赖性的增加。与正常NLR组相比（1.48≤NLR <4.58），高NLR组（NLR≥4.58）的尾巴DNA百分比更高。此外，在所有工人中，NLR和％尾巴DNA之间存在显着且正相关的关系，％尾巴DNA介导了15％的铅对NLR增加的影响。

结论

我们的大规模人群研究表明，铅的暴露会增加NLR并引起遗传毒性。NLR升高与DNA损伤之间存在关联。此外，％尾巴DNA对BLL与NLR之间关系的介导作用提供了机械证据，表明某些机制（例如炎症）可能与铅暴露引起的NLR升高有关。因此，NLR可能是指示Pb毒性的便捷且敏感的生物标记。需要进一步的研究来验证提议的机制和NLR作为生物标记。